INTERNATIONAL JOURNAL OF

ENVIRONMENTAL RESEARCH
AND PUBLIC HEALTH

Article
Sleep Disturbance in Adjustment Disorder
and Depressive Episode
1,2,3, 1,4 1,5
Anne M. Doherty *, Louisa Lorenz , Faraz Jabbar , Eamonn O’Leary
6 1
and Patricia Casey
1 Department of Adult Psychiatry, UCD School of Medicine and Medical Science, University College Dublin,
Mater Misericordiae University Hospital, 62/63 Eccles Street, 7 Dublin, Ireland;
l.lorenz@psychologie.uzh.ch (L.L.); Faraz.jabbar@ubc.ca (F.J.); profcasey@esatclear.ie (P.C.)
2 Department of Psychiatry, University Hospital Galway, H91 YR71 Galway, Ireland
3 Department of Psychiatry, National University of Ireland, Galway, Newcastle, H91 TK33 Galway, Ireland
4 Psychologisches Institut, University of Zurich, Rämistrasse 71, CH-8006 Zürich, Switzerland
5 Department of Psychiatry, University Hospital of Northern British Columbia, 1444 Edmonton Street,
Prince George, BC V2M6W5, Canada
6
National Cancer Registry Ireland, Building 6800, Cork Airport Business Park, Kinsale Road, Cork T12
CDF7, 021 Cork, Ireland; e.oleary@ncri.ie
* Correspondence: anne.doherty5@hse.ie or annedohertyemail@gmail.com; Tel.: +353-9154-3984

Received: 28 January 2019; Accepted: 21 March 2019; Published: 26 March 2019

Abstract: Background: In this paper, we aimed to examine the patterns of sleep disturbance in
adjustment disorder (AD) and depressive episode (DE), to examine the variables associated with sleep
disturbance in AD and DE and associated impairment in functioning. Methods: This is a multi-centre
case-control study of 370 patients: 185 patients with AD and 185 patients with a diagnosis of DE,
recruited from the liaison psychiatry services of three Dublin hospitals. We examined the participants’
sleep pathology using the sleep disturbance items on the Schedule for Clinical Assessment in
Neuropsychiatry, and the Inventory of Depressive Symptoms—Clinician-rated-30. Results: Patients with
a diagnosis of AD were less likely to report disturbed sleep than those with a diagnosis of DE (p =
0.002). On multivariate analysis, sleep disturbance was significantly associated with greater severity of
certain depressive symptoms: decreased appetite (p < 0.001) and psychomotor agitation (p = 0.009).
Decreased appetite, younger age and single marital status were significantly associated with sleep
disturbance in male patients, and decreased appetite and psychomotor agitation were significantly
associated with sleep disturbance in female participants. Conclusions: This is the largest study to date
which has examined sleep disturbance in adjustment disorder. Disturbance of sleep is a significant
symptom in AD and may represent a potential target for treatment. With further research, patterns of
sleep disturbance may be useful in differentiating AD from DE.

Keywords: adjustment disorder; depressive episode; sleep initiation and maintenance disorders;
liaison psychiatry; diagnosis; sleep

1. Introduction
Sleep disturbance is a common symptom of many psychiatric disorders and is included as a
diagnostic criterion in many conditions, most notably depressive episode (DE) [1]. Adjustment disorder
(AD) is defined by the World Health Organisation (WHO) in the tenth edition of The International
Classification of Diseases: Classification of Mental and Behavioural Disorders (ICD-10) as a state of
“subjective distress and emotional disturbance, usually interfering with social functioning and
performance, and arising in the period of adaptation to a significant life change or to the consequences of
a stressful life event” [1]. A diagnosis of AD requires the presence of a precipitating stressor,

Int. J. Environ. Res. Public Health 2019, 16, 1083; doi:10.3390/ijerph16061083 www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2019, 16, 1083 2 of 11

resolution of symptoms within six months of the termination of the stressor and the absence of
another mental disorder. The ICD-10 diagnostic criteria do not specify the symptoms we expect to
see in AD beyond “those found in any of the affective disorders”, but some indication of this is given
in the sub-groupings of AD in ICD-10, where there are subcategories including “brief depressive
reaction”, “prolonged depressive reaction”, “mixed anxiety and depressive reaction” indicate the
common presentations of the condition [1]. Similarly, DSM-5 has categories “with depressed mood”,
“with anxiety” and “with mixed anxiety and depressed mood” [2]. Given that AD has symptomatic
overlap with depression and anxiety, it may be associated with sleep disturbance, although there is
little in the literature regarding this.
AD is a common disorder in liaison psychiatry [3]. It is a disorder which has attracted some
controversy regarding its role in the classification systems, and its nomenclature has undergone some
transformation over the past 60 years, although it has retained its key clinical characteristics. These
characteristics include symptoms common to those seen in both anxiety disorder and depressive
episode. Unlike those conditions where a list of required symptoms is provided, the classification systems
ICD-10 and DSM-5 do not provide a list of potential symptoms. It is well recognized that many of the
biological symptoms of depression are commonly seen in AD [4,5], and certain symptoms such as
suicidal ideation are equally common in both conditions [6]. Sleep is one of these symptoms, and to date
there has been little research specifically examining the role of sleep in AD, whether as a symptom or
indeed as a precipitant of other symptoms such as suicidal ideation.
Previous research has suggested that there may be significant differences in risk variables and
in socio-demographic profile between those with a diagnosis of DE and those with a diagnosis of AD
[7,8]. These have not identified sleep as a symptom associated with the diagnosis of AD, although it
appears that sleep was not considered in these studies. Chellappa found an association between
insomnia and increased suicidality in depressed patients [9]. Cheung, in a population of Taiwanese
adolescents, found that sleep was associated with both major depression and AD but not directly
associated with suicidal ideation [10].
Zimmerman found that patients with a diagnosis of AD reported more insomnia compared with
those with a diagnosis of DE [11]. Mezzich found that depressive symptoms (including sleep
disturbance) were more common in DE than AD, but more common in AD than in individuals with no
diagnosis [12]. Lijun et al. likewise found that DE had a stronger association with sleep disturbance
than AD, but despite this, those with AD had more significant early wakening [13].
Several studies have reported an association between certain life events including workplace
difficulties and racial discrimination with sleep disturbance, but these studies were symptom-based
and did not use a formal diagnosis of AD, or indeed any diagnosis of any mental disorder [14–16].
Pillai found an association with poor adaptation to stress and insomnia, but again, no formal
diagnosis was used [17]. Lallukka found a significant relationship between sleep disturbance
requiring hypnotic medications and stress related to family or work conflicts in women [18].
In this study we aimed to examine the patterns of sleep disturbance in AD in comparison to DE
to study the variables associated with sleep disturbance in each diagnosis and to examine the
relationship between sleep disturbance and disturbance in functioning.
Our hypothesis is that patients with AD are as likely to suffer from sleep disturbance as those
with a diagnosis of a DE, and that there is no difference in the patterns of sleep disturbance
between the two conditions.

2. Materials and Methods

The methods of this study have been previously described in detail and are summarized briefly here
[19]. Participants were recruited from patients referred to the liaison psychiatry services at three Dublin
hospitals and diagnosed by the liaison psychiatrists with either a DE or AD. Patients were excluded if they
had a substance abuse disorder, cognitive impairment, psychotic symptoms, were
Int. J. Environ. Res. Public Health 2019, 16, 1083 3 of 11

under 18 or unable to give informed consent. Participants were interviewed at time of diagnosis,
and again after six months, for stability of diagnosis.
In examining sleep, the sleep disturbance items on the Schedule for Clinical Assessment in
Neuropsychiatry (SCAN) version 2, and the Inventory of Depressive Symptoms—Clinician-rated-30
(IDS-C30) were used [20,21]. SCAN is a semi-structured interview schedule created by the WHO
and the gold standard in the diagnosis and measurement of mental illness [20]. Specifically, we
used question 8.009 from SCAN, which examined sleep disturbance globally asking: “Have you had
any trouble with sleep in the past 2 weeks?”. This is endorsed if the participant reported disturbed
sleep in the preceding two weeks. For the variable of decreased function, we used ‘interference with
activities due to sleep problems’ in SCAN (variable 8.021: “How much interference has there been
with your everyday activities because of your problems sleeping?”). This is endorsed where the
patient reported that sleep disturbance is causing the functional problems.
Both of these variables are rated on a scale from 0 to 3, scoring 0 if there is a “positive rating of
absence”, scoring 1 where a symptom is present but to “such a minor degree that it is not appropriate for
use in classification”, scoring 2 where the symptom “is present to a level sufficient to use in
classification”, and a score of 3 is given where “the symptom is present in severe form for most of the
period”. For logistic regression we divided the participants into those without the symptom (scoring 0 or 1)
and compared them with those participants who endorsed the symptoms (scoring 2 or 3).
IDS-C30 was used to measure overall depressive symptoms [21]. It is a clinician administered
30 item scale, which is used to examine specific depressive symptoms in detail, each of which is
rated on a scale of 0–3. It has a high level of internal consistency with a Cronbach’s alpha of 0.892.
We used the first four questions of IDS-C30, which examine specific types of sleep
disturbance: “sleep onset insomnia”, “middle insomnia”, “early morning insomnia” and
“hypersomnia”, each on a scale 0–3 [21]. Sleep onset insomnia was scored 0 if the participant
“never takes longer than 30 min to fall asleep”, scored 1 if the participant “takes at least 30 min to fall
asleep, less than half the time”, scored 2 if the participant “takes at least 30 min to fall asleep, more
than half the time”, and scored 3 if the participant “takes at least 60 min to fall asleep, more than half
the time”. Mid-nocturnal insomnia was scored 0 if the participant “does not wake up at night”, scored
1 if the participant reports a “restless, light sleep with few awakenings”, scored 2 if the participant
“wakes up at least once a night, but goes back to sleep easily”, and scored 3 if the participant
“wakes up more than once a night and stays awake for 20 min or more, more than half the time”.
Early morning insomnia was scored 0 if the participant “less than half the time, awakens no more
than 30 min before necessary”, scored 1 if the participant: “more than half the time, awakens more
than 30 min before need be”, scored 2 if the participant “awakens at least one hour before need be,
more than half the time,”, and scored 3 if the participant “awakens at least two hours before need be,
more than half the time”. Hypersomnia was scored 0 if the participant “sleeps no longer than 7–8
h/night, without naps”, scored 1 if the participant “sleeps no longer than 10 h in a 24 h period
(include naps)”, scored 2 if the participant “sleeps no longer than 12 h in a 24 h period (include
naps)” and scored 3 if the participant “sleeps longer than 12 h in a 24 h period (include naps)”.
We explored the relationship of disturbed sleep to diagnosis, depressive symptoms and other
variables related to this relationship, including life events, social functioning and personality. In
multivariate analysis, for depressive symptoms we used the total score of IDS-C30, minus those
scores derived from the sleep items [21].
The power calculations performed were based on methods described by Smith and Morrow [ 22]. To
have 95% confidence of detecting a difference in depressive symptomatology of similar magnitude to that
detected in Casey et al. [23], at a significance level of p < 0.05, we required 185 individuals with AD and
185 individuals with DE. Statistics were calculated using SPSSv24 [24]. Univariate analysis was conducted
using an independent samples t-test, Mann-Whitney U test and chi-square test. The outlier analysis using the
Mahalanobis distance detected no multivariate outliers in the data. Multivariate analysis was conducted
using logistic regression with the variables disturbance of sleep
Int. J. Environ. Res. Public Health 2019, 16, 1083 4 of 11

and impairment of function as the binary dependent variables respectively, as described above. The
independent variables entered into each model were sex, age, marital status and those variables
which were found to have a significant association with the dependent variable. We decided to
combine the two diagnostic categories in order to examine sleep disturbance and related functional
impairment in the population as a whole, as this study was underpowered for this post hoc analysis.
Ethical approval was granted by the Mater University Hospital Research Ethics Committee
Ref/1/378/1146.

3. Results
A total of 370 patients were recruited to this study. Of these, 185 (50%) had a diagnosis of AD;
the remainder were diagnosed with DE. A majority, 235 (63.5%) participants were female. The
average age was 43.8 years (SD 14.2), and the mean age of patients with a diagnosis of AD were
older (but not significantly older) than those diagnosed with DE. There were no significant
differences between the two diagnostic groups in the socio-demographic variables of gender and
marital status. Patients with a diagnosis of AD were significantly less likely to report disturbed sleep
than those with a diagnosis of DE (Table 1). There were no significant differences in early onset
sleep disturbance or oversleeping, but mid-nocturnal sleep disturbance and early wakening were
significantly more commonly reported in patients with a diagnosis of DE, who were likewise
significantly more likely to report disturbance of functioning due to sleep problems than those with
AD. Patients with AD were significantly less likely (p < 0.001) to have been prescribed hypnotics.
When we examined the patterns of disturbed sleep by gender, there were no significant differences
between male and female participants in this study (Supplementary Table S1).

Table 1. Demographic and clinical characteristics of patients divided by diagnosis.

Characteristics Total Adjustment Depressive p Value

Disorder Episode
Age Mean (SD) 43.8 (14.2) 43.5(14.5) 44.1 (13.9) a
0.676
Gender Male (%) 135 (36.5) 66 (48.9) 69 (51.1) b
0.746
Female (%) 235 (63.5) 119 (50.6) 116 (49.4)
Single, n (%) 131 (36.0) 65 (35.5) 66 (36.4)
b
Marital Status Married/Cohabiting, n (%) 163 (44.8) 78 (42.6) 85 (47.9) 0.422
Sep/Div/Widowed, n (%) 70 (19.2) 40 (21.9) 30 (16.6)
Depressive symptoms: mean Mean (SD) 34.9 (12.7) 30.8(12.3) 38.8 (11.9) a
<0.001
IDS-C30 total score, range 0–90
Depressive symptoms: mean a
<0.001
IDS-C30 total score minus sleep Mean (SD) 30.1 (11.0) 26.6(10.6) 33.5 (10.4)
item, range 0–78%
Sleep disturbance, range 0–3 * Mean (SD) 1.5 (1.0) 1.4 (1) 1.7 (0.9) a
0.002
Impairment of function, Mean (SD) 1.1 (0.9) 0.9(0.8) 1.3 (0.9) a
<0.001
range 0–3 *
Early insomnia, range 0–3% Mean (SD) 1.6 (1.1) 1.5(1.1) 1.7 (1) a
0.251
Mid nocturnal insomnia, Mean (SD) 1.6 (1.1) 1.4(1.1) 1.7 (1) a
0.003
range 0–3%
Early wakening, range 0–3% Mean (SD) 1.4 (1.2) 1.1(1.1) 1.6 (1.1) a
<0.001
Hypersomnia, range 0–3% Mean (SD) 0.3 (0.6) 0.2(0.6) 0.3 (0.7) a
0.072
Hypnotic use N (%) 135 (38.8) 46 (26.6) 89 (50.9) b
<0.001
a b % variables from Inventory of Depressive
= Independent samples t-test; = chi square;
Symptoms—Clinician-rated-30 (IDS-C30), higher scores denote greater symptoms burden; * variables from the
Schedule for Clinical Assessment in Neuropsychiatry (SCAN), higher scores denote greater symptoms burden.

When participants who reported disturbed sleep were compared to those who did not, the group
with disturbed sleep reported significantly more depressive symptoms and were significantly more likely
to have a diagnosis of DE rather than AD (Table 2). They were significantly more likely to report other
depressive symptoms as measured by the IDS-C30 including disturbance of mood, decreased
Int. J. Environ. Res. Public Health 2019, 16, 1083 5 of 11

appetite, decreased concentration, negative outlook towards self and future, poor energy,
decreased enjoyment, reduced sexual interest, psychomotor agitation and leaden paralysis. They
had higher mean scores on the IDS-C30, indicating a greater burden of depressive symptoms.

Table 2. Demographic and clinical characteristics of patients divided by sleep disturbance.

Total Sleep No Sleep

Characteristics Disturbance * Disturbance * p Value
n = 344
n = 181 n = 163
Age Mean (SD) 43.6 (14.3) 43.5 (13.9) 43.7 (14.9) a
0.865
Gender Male (%) 120 (34.9) 70 (38.7) 50 (30.7) b
0.120
Female (%) 224 (65.1) 111 (61.3) 113 (69.3)
Single, n (%) 119 (35.2) 64 (36.2) 55 (34.2)
Marital Status b
Married/Cohabiting, n (%) 155 (45.9) 78 (44.1) 77 (47.8) 0.781
Sep/Div/Widowed, n (%) 64 (18.9) 35 (19.8) 29 (18.0)
Depressive symptoms: mean Mean (SD) 34.9 (12.7) 40.2 (11.4) 29 (11.4) a
<0.001
IDS-C30 total score, range 0–90%
Depressive symptoms: mean a
<0.001
IDSC-30 total minus sleep items, Mean (SD) 30.1 (11) 34.2 (10.3) 25.6 (10.1)
range 0–78%
Clinical diagnosis Adjustment Disorder (%) 172 (50) 77 (42.5) 95 (58.3) b
0.004
Depressive episode (%) 172 (50) 104 (57.5) 68 (41.7)
Other depressive symptoms from a
0.002
IDS-C30% Mean (SD) 1.9 (0.9) 2.0 (0.8) 1.7 (0.9)
Mood sad
Mood irritable Mean (SD) 1.5 (0.9) 1.6 (0.8) 1.2 (0.9) a
<0.001
Mood anxious Mean (SD) 1.7 (0.9) 1.8 (0.9) 1.4 (0.9) a
<0.001
Reactivity of mood Mean (SD) 1.1 (0.9) 1.2 (0.9) 0.9 (0.9) a
0.003
Mood variation Mean (SD) 0.9 (1.0) 1.0 (1.0) 0.8 (1.0) a
0.112
Mood worse in morn Mean (SD) 0.5 (0.8) 0.4 (0.7) 0.7 (0.9) a
0.003
Mood variation due to environment Mean (SD) 0.3 (0.5) 0.3 (0.5) 0.3 (0.5) a
0.142
Quality of mood Mean (SD) 1.4 (1.0) 1.4 (0.9) 1.2 (1.1) a
0.057
Appetite decreased Mean (SD) 1.0 (0.9) 1.2 (0.9) 0.7 (0.9) a
<0.001
Appetite increased Mean (SD) 0.3 (0.9) 0.3 (0.9) 0.4 (1.0) a
0.211
Weight decrease 2 weeks Mean (SD) 0.7 (0.9) 0.7 (0.9) 0.6 (1.0) a
0.431
Weight increase 2 weeks Mean (SD) 0.3 (0.7) 0.3 (0.6) 0.4 (0.9) a
0.105
Concentration/decision making Mean (SD) 1.5 (0.8) 1.6 (0.8) 1.3 (0.8) a
0.001
Outlook self Mean (SD) 1.3 (1.0) 1.4 (1.0) 1.1 (0.9) a
0.016
Outlook future Mean (SD) 1.6 (0.9) 1.7 (0.9) 1.5 (0.9) a
0.025
Involvement Mean (SD) 1.6 (0.9) 1.7 (0.9) 1.4 (1.0) a
0.008
Energy/fatigeability Mean (SD) 1.7 (1.0) 1.6 (0.8) 1.3 (0.9) a
0.028
Pleasure/enjoyment Mean (SD) 1.5 (0.9) 1.6 (0.8) 1.3 (0.9) a
0.009
Sexual interest Mean (SD) 1.7 (1.0) 1.8 (0.9) 1.4 (1.0) a
<0.001
Psychomotor slowing Mean (SD) 0.6 (0.7) 0.6 (0.8) 0.6 (0.7) a
0.895
Psychomotor agitation Mean (SD) 0.8 (0.8) 0.8 (0.8) 0.6 (0.7) a
0.002
Somatic complaints Mean (SD) 0.9 (0.8) 0.9 (0.9) 0.9 (0.8) a
0.488
Sympathetic arousal Mean (SD) 0.8 (0.9) 0.8 (0.8) 0.8 (1.2) a
0.854
Panic/phobic symptoms Mean (SD) 0.9 (0.9) 1.0 (0.9) 0.8 (0.8) a
0.061
GIT Mean (SD) 0,7 (0.9) 0.7 (1.0) 0.6 (0.7) a
0.9
Interpersonal sensitivity Mean (SD) 1.5 (0.9) 1.5 (1.0) 1.4 (0.8) a
0.074
Leaden paralysis Mean (SD) 1.2 (0.9) 1.4 (0.9) 1.0 (0.8) a
0.001
a b
= Independent samples t-test; = chi square; * Schedule for Clinical Assessment in Neuropsychiatry (SCAN),
variable 8.009; % variables from the Inventory of Depressive Symptoms—Clinician-rated-30 (IDS-C30): higher
scores denote greater symptoms burden.

Participants who reported disturbance of function due to disturbed sleep reported significantly more
depressive symptoms compared with those who did not report disturbance of functioning. They
Int. J. Environ. Res. Public Health 2019, 16, 1083 6 of 11

were significantly more likely to have a diagnosis of DE rather than AD. They had higher mean scores on
IDS-C30, indicating a greater burden of depressive symptoms. They were significantly more likely to
report other depressive symptoms as measured by the IDSC-C30 including disturbance of mood,
decreased appetite, decreased concentration, negative outlook towards self and future, poor energy,
decreased enjoyment, reduced sexual interest and interpersonal sensitivity (Table 3).

Table 3. Demographic and clinical characteristics of patients divided by disturbance in function

attributed to sleep difficulties.

Functional No Functional
Characteristics Total Difficulties Due to Problems Due to p Value
n = 345 Sleep Disturbance Sleep Disturbance
* n = 137 * n = 208
Age Mean (SD) 43.6 (14.3) 43.5(14.5) 43.7 (14.3) a
0.921
Gender Male n (%) 122 (35.4) 50 (36.5) 72 (34.6) b
0.721
Female n (%) 223 (64.6) 87 (63.5) 136 (65.4)
Single, n (%) 119 (35.1) 43 (32.1) 76 (37.1)
Marital Status Married/Cohabiting, n (%) 155 (45.7) 64 (47.8) 91 (44.4) b
0.643
Sep/Div/Widowed, n (%) 65 (19.2) 27 (20.1) 38 (18.5)
Depressive symptoms: mean Mean (SD) 35 (12.6) 39.2(12.4) 32.3 (12) a
<0.001
IDS-C30 total score, range 0–90%
Depressive symptoms: mean a
<0.001
IDS-C30 total score minus sleep Mean (SD) 30.2 (11) 33.7(10.7) 27.9 (10.5)
item, range 0–78%
Clinical diagnosis Adjustment Disorder (%) 175 (50.7) 49 (35.8) 121 (58.2) b
<0.001
Depressive episode (%) 172 (50) 104 (57.5) 68 (41.7)
Other depressive symptoms from a
<0.001
IDS-C30% Mean (SD) 1.9 (0.9) 2.2(0.8) 1.7 (0.9)
Mood sad
Mood irritable Mean (SD) 1.5 (0.9) 1.8(0.8) 1.3 (0.9) a
<0.001
Mood anxious Mean (SD) 1.7 (0.9) 1.9(0.9) 1.5 (0.9) a
<0.001
Reactivity of mood Mean (SD) 1.1 (0.9) 1.3(0.9) 1.0 (0.9) a
0.014
Mood variation Mean (SD) 0.9 (1.0) 1.1(1.1) 0.8 (1.0) a
0.017
Mood worse in morn Mean (SD) 0.5 (0.8) 0.3(0.7) 0.6 (0.8) a
0.003
Mood variation due to environment Mean (SD) 0.3 (0.5) 0.2(0.4) 0.3 (0.5) a
0.079
Quality of mood Mean (SD) 1.4 (1.0) 1.5(0.9) 1.3 (1.0) a
0.011
Appetite decreased Mean (SD) 1.0 (0.9) 1.3(0.9) 0.8 (0.9) a
<0.001
Appetite increased Mean (SD) 0.3 (0.9) 0.2(0.9) 0.4 (0.9) a
0.165
Weight decrease 2 weeks Mean (SD) 0.7 (0.9) 0.7(0.9) 0.7 (1.0) a
0.916
Weight increase 2 weeks Mean (SD) 0.3 (0.7) 0.2(0.6) 0.4 (0.8) a
0.052
Concentration/decision making Mean (SD) 1.5 (0.8) 1.7(0.7) 1.4 (0.8) a
0.001
Outlook self Mean (SD) 1.3 (1.0) 1.5(1.0) 1.2 (0.9) a
0.003
Outlook future Mean (SD) 1.6 (0.9) 1.8(0.9) 1.5 (0.9) a
0.003
Involvement Mean (SD) 1.6 (0.9) 1.8(0.9) 1.4 (0.9) a
<0.001
Energy/fatiguability Mean (SD) 1.7 (1.0) 1.9(0.8) 1.6 (0.8) a
<0.001
Pleasure/enjoyment Mean (SD) 1.5 (0.9) 1.7(0.9) 1.3 (0.8) a
<0.001
Sexual interest Mean (SD) 1.7 (1.0) 1.9(0.9) 1.6 (1.0) a
0.004
Psychomotor slowing Mean (SD) 0.6 (0.7) 0.6(0.8) 0.6 (0.7) a
0.856
Psychomotor agitation Mean (SD) 0.8 (0.8) 1.0(0.9) 0.6 (0.8) a
<0.001
Somatic complaints Mean (SD) 0.9 (0.8) 1.0(0.9) 0.9 (0.8) a
0.328
Sympathetic arousal Mean (SD) 0.8 (0.9) 0.8(0.9) 0.7 (1.0) a
0.352
Panic/phobic symptoms Mean (SD) 0.9 (0.9) 1.0(0.9) 0.9 (0.9) a
0.286
GIT Mean (SD) 0,7 (0.9) 0.7(1.1) 0.6 (0.7) a
0.331
Interpersonal sensitivity Mean (SD) 1.5 (0.9) 1.6(1.0) 1.4 (0.9) a
0.038
Leaden paralysis Mean (SD) 1.2 (0.9) 1.3(1.0) 1.2 (0.9) a
0.332
= Independent samples t-test; b = chi square; * Schedule for Clinical Assessment in Neuropsychiatry (SCAN), variable 8.021; %
a
variables from the Inventory of Depressive Symptoms—Clinician-rated-30 (IDS-C30): higher scores denote greater symptoms
burden.
Int. J. Environ. Res. Public Health 2019, 16, 1083 7 of 11

On multivariate analysis, where sleep disturbance was the dependent variable, it was significantly
associated with the following specific depressive symptoms: decreased appetite, and psychomotor in the
study population as a whole, after controlling for age, gender and marital status (Table 4). We decided to
combine the two diagnostic categories in order to examine sleep disturbance and related functional
impairment in the population as a whole, as when treated separately, the findings were non-significant,
probably due to this study being underpowered for this post hoc analysis.

Table 4. Multivariate analysis: logistic regression, with sleep disturbance as the dependent binary
variable, in AD and DE combined (i.e., the entire sample).

Total Male (n = 135) Female (n = 235)

p B CI p B CI p B CI
Age 0.218 0.002 0.006–0.001 0.013 0.059 0.900–0.988 0.440 0.012 0.959–1.018
Gender 0.767 0.015 0.115–0.085 - - - - - -
Marital status 0.155 0.024 0.012–0.077 0.002 2.956 0.008–0.350 0.783 0.117 0.387–2.045
Clinical 0.101 0.084 0.016–0.184 0.851 0.144 0.193–3.893 0.087 0.788 0.184–1.122
diagnosis
Depressed 0.394 0.029 0.044–0.101 0.197 0.637 0.719–4.975 0.655 –0.136 0.480–1.587
mood %
Decreased <0.001 0.103 0.048–0.159 0.009 1.546 1.462–15.119 0.009 0.794 1.217–4.019
appetite %
Outlook for 0.979 0.001 0.062–0.063 0.706 0.155 0.522–2.614 0.956 0.016 0.565–1.716
future %
Energy % 0.492 0.022 0.094–0.05 0.174 0.646 0.752–4.836 0.832 0.066 0.506–1.729
Pleasure/ 0.431 0.032 0.112–0.048 0.810 0.138 0.371–3.551 0.149 0.472 0.845–3.043
enjoyment %
Sexual 0.098 0.059 0.003–0.12 0.910 0.050 0.398–2.271 0.570 0.146 0.7–1.911
interest %
Psychomotor 0.009 0.077 0.017–0.137 0.459 0.331 0.580–3.342 0.181 0.341 0.432–1.171
agitation %
Leaden 0.061 0.062 0.001–0.124 0.399 0.394 0.270–1.686 0.191 0.402 0.819–2.728
paralysis %
% variables from IDS-C30, higher scores denote greater symptom burden.

When the sample was divided by gender, there were differences between the male and female
participants. Among female participants, decreased appetite and psychomotor agitation were
associated with sleep disturbance. Among male participants, younger age, single marital status and
decreased appetite were associated with sleep disturbance.
We performed multivariate analysis with disturbance of function due to disturbed sleep as the
dependent variable. In the population as a whole, it was significantly associated with a diagnosis of
DE and single marital status, and with the following specific depressive symptoms: decreased
appetite, decreased energy and psychomotor agitation, after controlling for age and gender (Table
5). When the sample was divided by gender, there were differences between the male and female
participants. Among female participants, a clinical diagnosis of DE, low mood, decreased appetite and
reduced enjoyment were associated with greater impairment of function attributed to sleep disturbance.
Among male participants, younger age, decreased appetite, psychomotor agitation and reduced leaden
paralysis were associated with sleep disturbance.
Int. J. Environ. Res. Public Health 2019, 16, 1083 8 of 11

Table 5. Multivariate analysis: logistic regression, with disturbance in function due to sleep problems
as the dependent binary variable, in AD and DE combined (i.e., the entire sample).

Total Male (n = 135) Female (n = 235)

p B CI p B CI p B CI
Age 0.716 0.001 0.008–0.005 0.412 0.014 0.954–1.020 0.846 0.002 0.98–1.025
Gender 0.963 0.004 0.182–0.191 - -
Marital status 0.038 0.089 0.005–0.173 0.293 0.529 0.220–1.579 0.831 0.070 0.492–1.766
Clinical <0.001 0.365 0.179–0.551 0.284 0.564 0.203–1.595 0.001 1.174 0.159–0.600
diagnosis
Depressed 0.095 0.115 0.02–0.25 0.147 0.533 0.285–1.207 0.004 0.766 1.283–3.608
mood %
Decreased 0.005 0.149 0.046–0.252 0.010 0.743 1.193–3.702 0.054 0.338 0.994–1.977
appetite %
Outlook for 0.294 0.062 0.052–0.179 0.252 0.375 0.766–2.762 0.533 0.130 0.585–1.320
future %
Energy % 0.038 0.142 0.008–0.276 0.064 0.806 0.955–5.255 0.117 0.364 0.913–2.269
Pleasure/ 0.654 0.004 0.145–0.154 0.007 1.391 1.467–11.017 0.048 0.511 0.362–0.995
enjoyment %
Sexual 0.329 0.057 0.171–0.058 0.052 0.764 0.215–1.007 0.307 0.201 0.831–1.800
interest %
Psychomotor 0.001 0.19 0.078–0.301 0.002 1.085 1.479–5.92 0.069 0.349 0.973–2.067
agitation %
Leaden 0.716 0.001 0.008–0.005 0.036 0.612 0.306–1.579 0.836 0.044 0.632–1.450
paralysis %
% variables from IDS-C30, higher scores denote greater symptom burden.

4. Discussion
In examining the patterns of sleep disturbance in AD and DE, we found that certain symptoms
were equally common in both conditions, namely “sleep onset insomnia” and “hypersomnia”, while
others (middle insomnia and early morning insomnia) were more common in DE. Depressive
symptoms were significantly associated with sleep disturbance in the two diagnostic groups, both
combined and separately. On multivariable analysis, decreased appetite and psychomotor agitation
were associated with sleep disturbance. A diagnosis of DE, decreased appetite, decreased energy
and psychomotor agitation were associated with impairment of function due to disturbed sleep.
We found that sleep disturbance was associated with different variables in male and female
individuals with adjustment disorder or depression in a liaison psychiatry setting. Decreased appetite was
significantly associated with sleep disturbance in both genders. As both disturbance of sleep and
disturbance of appetite are important biological symptoms of depression, this is not unexpected [1,2]. In
addition, younger age and single marital status were associated with sleep disturbance in male patients,
and psychomotor agitation was significantly associated with sleep disturbance in female participants.
These findings have not previously been examined in the literature and our findings suggest that for
females with AD and DE, symptoms of depression are most associated with sleep disturbance, whereas
psychosocial variables have a greater impact in males with AD and DE.
Decreased appetite was likewise significantly associated with impairment of functioning attributable
to sleep disturbance in both genders. In addition, a clinical diagnosis of DE, low mood, and reduced
enjoyment were significantly associated with impairment of functioning attributable to sleep disturbance in
female participants, and younger age, psychomotor agitation and reduced leaden paralysis were
associated with impairment of functioning attributable to sleep disturbance in male patients. These
findings are consistent with existing evidence which has demonstrated gender-based differences in the
covariates of both sleep disturbance and associated functional impairment [25,26]. Like Chasens et al., we
found significant gender-based expression of impaired sleep on functional
Int. J. Environ. Res. Public Health 2019, 16, 1083 9 of 11

outcomes [25]. Previous work by Hyde has suggested that any gender-based differences in
functional impairment due to sleep disturbance were likely to be small [27]. In contrast to Hyde, it is
difficult to comment on the strength of these differences given that the study was not powered for
these post hoc analyses.
With respect to our hypothesis, that patients with AD are as likely to suffer from sleep disturbance
as those with a diagnosis of DE, we found that sleep disturbance is common in both conditions but
significantly more common in DE. We found that a diagnosis of DE was associated with sleep
disturbance in females, but that there was no difference between the two diagnoses in males.
This study confirms that sleep disturbance is a common symptom in AD and one which is
associated with significant disturbance of functioning. It also indicates gender-related differences in
this cohort of patients with low mood attending a liaison psychiatry service. No previous study has
examined the patterns of sleep disturbance in this level of detail: indeed, only two have examined
sleep disturbance in AD at all, and these studies have produced conflicting evidence. Like
Zimmerman, we found significant degrees of reported sleep disturbance in AD, and like Mezzich,
we found greater symptom severity in DE compared with AD [11,12]. Certain symptoms were
similarly common in both conditions, such as sleep onset insomnia and hypersomnia. Others,
insomnia and early morning insomnia, were more common in DE. The association of functional
impairment attributable to disturbed sleep with specific depressive symptom severity in AD and DE
on multivariable testing has not been previously demonstrated.
This study is one of few which have examined the association of AD with sleep disturbance,
and the first to examine the sleep pattern seen in AD and to investigate the other variables
associated with both sleep disturbance and functional impairment associated with sleep
disturbance. It is one of the first to examine gender related differences in sleep in a cohort of
patients with AD. This study included a large number of patients with AD: the relatively large sample
size derived from our power calculations. This is the largest study yet to have been conducted
examining sleep disturbance in patients with AD and DE. Previous studies examining the
relationship between AD and sleep have been of smaller sample size [28]. This study used
instruments which have been validated in similar populations to assess a broad range of parameters
including depressive symptoms [21], which allowed us to control for a wide range of confounding
variables. A systematic review found that sleep disturbance is associated with increased suicidal
behaviour, and although this was not a finding of our study, it is an important target for treatment in
people with impairment of psychosocial function in adjustment disorder [29]. No previous studies
have examined gender-based differences in sleep disturbance in AD.
The limitations of this study include the use of clinical diagnosis. We chose the clinical diagnosis
from the two options available (clinical diagnosis and SCAN diagnosis) as the gold standard for the
purpose of this study. Clinical diagnoses are informed by the ICD-10 diagnostic guidelines in a broad
fashion and take into account the context within which symptoms arise. This optimizes the applicability of
findings to everyday clinical practice. Unlike clinical diagnosis, SCAN diagnosis looks at symptoms only,
without taking account of context, and context is essential in making a diagnosis of AD. We expected that
as a result of this inherent flaw in the diagnostic instruments, the use of SCAN would result in a conflation
of AD with DE, and as a result would not be useful in distinguishing between the two diagnoses [ 5]. In our
comparison of the two diagnoses this proved to be well-founded, as 73.4% of those participants with a
clinical diagnosis of AD were diagnosed with DE using SCAN, resulting in a sensitivity of 91.8% and a
specificity of 57.2%. The heterogeneity of clinical presentation in AD, including fluctuating psychological
symptoms, behavioural disturbances and physical symptoms which can characterize certain clinical
presentations with AD, adds to the complexity of this diagnosis [28]. Other limitations include the small
numbers with sleep disturbance.
Finally, participants were recruited from a consultation-liaison psychiatry population in two general
hospitals and one maternity hospital. While this might be regarded as limiting the generalizability of findings
to this population and being of less relevance to other populations such as
Int. J. Environ. Res. Public Health 2019, 16, 1083 10 of 11

community-based mental health services or primary care, it has the merit of focusing on a
population in which AD is particularly common and thus is well appointed to provide useful
information for consultation-liaison psychiatry teams [29]. This diversity of participants also spans
the full range of severity, from less severe cases treated as outpatients to more severe cases
presenting to the emergency department with acute and severe symptoms.
This paper is novel in its examination of the disturbance of sleep which occurs not only in DE,
but also in AD. We have demonstrated an association between sleep disturbance and other
depressive symptoms in both diagnostic groups and that where sleep disturbance is present,
patients report a greater severity of depressive symptoms, irrespective of diagnosis. Sleep
disturbance may represent a new focus for treatments such as cognitive behavioural therapy, which
has a strong evidence base in the treatment of sleep disturbance.

5. Conclusions
This study found that while sleep disturbance is more severe in DE, it is also common in AD
and is frequently associated with disturbance of function. It is a significant symptom in AD and one
which may be amenable to a behavioural approach, given that psychotropics have a poor evidence
base within this diagnostic group. Further research is required to identify if patterns of sleep
disturbance may be useful in the clinical challenge of differentiating AD from DE.

Supplementary Materials: The following are available online at http://www.mdpi.com/1660-4601/16/6/1083/

s1, Table S1: Demographic and clinical characteristics of patients divided by gender.
Author Contributions: Conceptualization: P.C., A.M.D., F.J.; methodology P.C., A.M.D., F.J.; software, P.C.,
A.M.D., E.O.; validation, P.C., A.M.D., E.O.; formal analysis, P.C., A.M.D., L.L., E.O.; investigation, P.C.,
A.M.D., F.J.; resources, P.C., A.M.D., F.J.; data curation, A.M.D., L.L., E.O.; writing—original draft preparation,
A.D.; writing—review and editing, P.C., A.M.D., L.L., F.J., E.O.; visualization, P.C., A.M.D., F.J.; supervision,
P.C.; project administration, A.M.D., F.J.
Funding: This research received no external funding.
Acknowledgments: We would like to acknowledge the support of Geraldine Byrne and Maura Costello.
Conflicts of Interest: The authors declare no conflicts of interest.

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